Molcular chaperones are conserved proteins that modulate intracellular protein folding. They bind to unfolded or partially folded polypeptides preventing misfolding and aggregation and promote folding, translocation, and the assembly and disassembly of multiprotein structures. A single cells can express a variety of chaperones, including representatives of the Hsp70, Hsp90 and Hsp60 families. These chaperones differ in their substrate preferences, oligomeric state, mode of action, and in eukaryotic organisms, their subcellular location. Among the chaperones, the Hsp70 family is of particular interest. Both prokaryotic and eukaryotic organisms have multiple Hsp70 proteins, and these proteins function in every cellular compartment of the eukaryotic cell. Each Hsp70 has a conserved 45 kD N-terminal ATPase domain followed by a 18 kD peptide binding domain and a less conserved C-terminal region. The X-ray structures of the two conserved domains have been determined separately, but there is no crystal structure of an intact Hsp70. Hsp70 proteins function in concert with a cochaperone, called DnaJ or Hsp40, which modulates the ATPase and substrate binding activities of Hsp70. Cells contain multiple DnaJ family members and, in some cases, a specific DnaJ is required for a particular Hsp70 to function. Despite the key role of DnaJ in Hsp70 function, little is known about how Hsp70 interacts with DnaJ at the level of structure. I propose to use Computer Graphics Lab facilities for modeling of Hsp70-DnaJ complex based on our recent finding that DnaJ binds to two sites in the E. coli Hsp70 protein, DnaK; one in its N- terminal ATPase domain and a second in its C-terminal peptide binding domain. Structural modeling will represent an important step forward in understanding both the functional regulation of Hsp70 by its co-chaperone DnaJ and many human diseases including bacterial infections, amylodosis, autoimmune isease and cancer that are involved in the function of Hsp70/DnaJ chaperone machine.